Ventilator-associated pneumonia (VAP) is the most costly and second most common hospital-acquired infection (HAI), accounting for over 86% of hospital-acquired pneumonia (HAP). Some 300,000 HAP patients are treated annually in the U.S., at an estimated annual hospital cost of more than $1.5 billion. The current paradigm for preventing VAP has been to implement patient care bundle practices and to use endotracheal tube (ETT) technologies that reduce bacterial access to and colonization on the tube surfaces. However, these strategies do not offer sustained inhibition of bacterial biofilm that is associated with VAP;their limited duration of efficacy hampers their value-particularly for late-onset VAP, which is more often associated with drug-resistant microbial species. Additionally, use of antimicrobial agents leads to resistance patterns that make infections more difficult to treat. By coating the tube surface, the risk of infection is reduced;however, this strategy at best only delays the infection onset. There are currently no definitive methods to prevent late-onset VAP associated with multi-drug-resistant pathogens. Sharklet Technologies therefore proposes to develop a novel ETT design capable of sustained biofilm inhibition that does not rely on traditional antibiotic coatings. Preliminary studies have shown that micro-patterns on polymer surfaces can be designed to inhibit bacterial biofilm-with the Sharklet" micro-pattern being the most effective. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize the use of the biomimetic Sharklet microscopic pattern to inhibit bacterial biofilm formation on the ETT lumen, cuff, and outer surfaces without the use of antimicrobial agents. The Specific Aims for Phase I are to 1) optimize performance of the Sharklet micro-pattern, and 2) test the most effective Sharklet micro-patterns for inhibition of biofilm formation with clinical isolates of the most common VAP causative pathogens in a mucin-modified growth media over the course of 14 days. (Previous projects have already proven the feasibility of manufacturing tubes with the Sharklet pattern on the inner or outer surfaces.) A follow-on Phase II project will be designed to develop scaled-up manufacturing methods for ETTs with Sharklet-patterned inner, outer, and cuff surfaces and to further demonstrate efficacy with an in vivo animal model. Additionally, Phase II will offer an opportunity to investigate a possible added benefit of a Sharklet-patterned ETT-reduced occlusion due to enhanced surface energy, which will be studied in an in vitro mucus occlusion model. The Phase I and Phase II SBIR data will be essential in attracting and fully engaging the types of "Phase III" private-sector investors and/or strategic partners with whom we are already discussing this technology. Phase III commercialization efforts will therefore be focused on establishing partnerships with medical device partners and distributors-particularly those in the ETT markets. PUBLIC HEALTH RELEVANCE: Every patient who receives mechanical ventilation via an endotracheal tube (ETT) is at risk for developing ventilator-associated pneumonia (VAP)-the second most common hospital-acquired infection, which has a high mortality rate and results in medical costs of some $1.5 billion annually in the U.S. alone. Given that an effective solution to this problem has not been developed, particularly for late-onset VAP, Sharklet Technologies, Inc., proposes to pursue the needed advance in the state-of-the-art by incorporating its Sharklet" microscopic pattern onto the ETT components to inhibit biofilm formation that leads to bacterial infections and to ultimately reduce the incidence of VAP. This multi-phase SBIR research effort is focused on developing/commercializing a Sharklet-patterned ETT that significantly augments current ETT designs with the goal of increasing patient welfare and safety while greatly reducing medical costs.